Wednesday, November 04, 2015

After more than three years of waiting, we finally have a (somewhat limited) case-control study on the MERS virus out of Saudi Arabia, and not surprisingly, it finds that among primary cases, recent dromedary exposure and certain comorbidities (diabetes, heart disease, smoking, etc.) are linked to acquiring the infection.

`Primary cases’ are those that occur in the community when there is no known exposure to a healthcare facility or to a known human case. Over the past 3 years, roughly 40% of Saudi cases are listed as either `primary’ or as from an undetermined origin.

Camel exposure has been assumed to account for some percentage of these cases, but the evidence for camel-to-human transmission has been relatively slim. Although it doesn’t answer all of our questions, today’s study does show a link between camel exposure and acquisition of the MERS virus.

As I mentioned, this is a limited study, conducted between March and November of 2014, during which time the Saudis identified 535 laboratory confirmed cases. Saudi testing has been largely limited to those with severe illness, so their surveillance may not have captured all of the cases during that time period.

By eliminating cases linked to hospital or household outbreaks, anyone who visited a healthcare facility in the two weeks prior to falling ill, or anyone who recalled exposure to someone with a respiratory illness (of any type), a subset of cases were identified with a presumed exposure to a`non-human’ contact.

After screening based on the exclusion criteria, 34 patients were identified as possible primary case-patients. Two persons refused to participate, and 2 did not meet the age criteria for inclusion. The remaining 30 case-patients, representing 8 of 13 regions in Saudi Arabia, were enrolled in the study

By using fairly stringent criteria, only about 5.6% of the cases during that time span `qualified’ for inclusion. Then 116 controls (based on age, gender, geographic location) were randomly selected, and then patients (or their proxies), and the controls were interviewed by teams of investigators.

The full study (which is well worth reading) is available online at the link below. I’ve only printed the abstract and a few excerpts. After you return, I’ll have a bit more.

Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset.

Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.

As mentioned earlier, while 40% of all Saudi MERS cases call into the `primary’ category, by applying very strict criteria designed to exclude possible human exposure, this study only looked at a subset of 5.6% of the cases during the study period.

Of the 30 patients selected, 33% reported camel contact in the 14 days prior to falling ill vs. 15% in the control group. While the numbers were small, being a household contact of someone who had camel contact (but who did not themselves fall ill) was also determined to be a risk factor.

Exposure to bats, goats, horses, sheep, or the products of these animals were not associated with MERS CoV illness with this study.

While the camel link is statistically significant, this obviously leaves a good many primary cases for which camel contact does not appear to be a factor. And that is not unexpected.

As MERS infection can sometimes produce only mild or subclinical illness, this has led to speculation there may be some limited `stealth’ transmission by unrecognized carriers in the community (see The Community Transmission Mystery).

The authors of this study acknowledge these non-camel related cases, and write:

Other potential explanations of MERS-CoV illness in primary case-patients who did not have direct contact with dromedaries include unrecognized community exposure to patients with mild or subclinical MERS-CoV infection or exposure to other sources of primary MERS-CoV infection not ascertained in our study. A recent nationwide serosurvey from Saudi Arabia estimated that >44,000 persons might be seropositive for MERS-CoV and might be the source of infection to patients with confirmed primary MERS-CoV illness but with no dromedary exposure (8).

Although we found that direct and indirect dromedary exposure were significantly associated with MERS-CoV illness, our study had limited power to detect specific behaviors or practices associated with illness. Future studies should be designed to further explore this association.

While certainly not responsible for all – or even a majority – of the primary MERS cases in Saudi Arabia, camel exposure does seem to be the source of sporadic re-introduction of the virus into the human population.

To date, the virus only transmits poorly outside of close quarters (like hospitals and households) and so interrupting this `reseeding’ of the virus into the community is a strategy likely to pay big dividends in the control of MERS. Getting camel owners to take the right kinds of precautions, however, has been met with considerable resistance.

As the authors state, this study is a good initial step in understanding how MERS transmits in the community, but we are still a long ways off from understanding the full picture.